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APOE 4 allele predicts faster cognitive decline in mild Alzheimer disease

From the Cognitive Neuroscience Division of the Gertrude H. Sergievsky Center (S.C., N.S., Y.S.), the Taub Institute for Research in Alzheimer's Disease and the Aging Brain (N.S., Y.S., E.H.), and the Department of Neurology (N.S., Y.S.), Columbia University Medical Center, New York; Department of Epidemiology (M.M.G.), Mailman School of Public Health, Columbia University, New York, NY; the Departments of Neurology (J.B., M.A.) and Psychiatry and Behavioral Sciences (J.B., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; and the Department of Psychiatry (D.B.), Massachusetts General Hospital, Harvard Medical School, Boston.

Address correspondence and reprint requests to Dr. Yaakov Stern, Columbia University Medical Center, 630 West 168th Street, P&S Box 16, New York, NY 10032 ys11{at}columbia.edu.

Objective: To determine whether APOE 4 predicts rate of cognitive change in incident and prevalent Alzheimer disease (AD).

Methods: Individuals were recruited from two longitudinal cohort studies—the Washington Heights and Inwood Columbia Aging Project (WHICAP; population-based) and the Predictors Study (clinic-based)—and were followed for an average of 4 years. Three samples of participants diagnosed with AD, with diverse demographic characteristics and baseline cognitive functioning, were studied: 1) 199 (48%) of the incident WHICAP cases; 2) 215 (54%) of the prevalent WHICAP cases; and 3) 156 (71%) of the individuals diagnosed with AD in the Predictors Study. Generalized estimating equations were used to test whether rate of cognitive change, measured using a composite cognitive score in WHICAP and the Mini-Mental State Examination in Predictors, varied as a function of 4 status in each sample.

Results: The presence of at least one 4 allele was associated with faster cognitive decline in the incident population-based AD group (p = 0.01). Parallel results were produced for the two prevalent dementia samples only when adjusting for disease severity or excluding the most impaired participants from the analyses.

Conclusion: APOE 4 may influence rate of cognitive decline most significantly in the earliest stages of Alzheimer disease.

Abbreviations: AD = Alzheimer disease; BDAE = Boston Diagnostic Aphasia Examination; CDR = Clinical Dementia Rating; DSM-III-R = Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition; ECT = electroconvulsive treatment; GCA = growth curve analysis; GEE = generalized estimating equations; HCFA = Health Care Finance Administration; MMSE = Mini-Mental State Examination; WHICAP = Washington Heights and Inwood Columbia Aging Project.

e-Pub ahead of print on April 9, 2008, at www.neurology.org.

Supported by federal grants AG0732, AG00261, RR00645, and R01AG007370.

Disclosure: Dr. Stern provides consultation to pharmaceutical companies unrelated to this study including Elan, Esai, and Wyeth. Drs. Cosentino, Scarmeas, Helzner, Glymour, Brandt, Albert, and Blacker report no conflicts of interest.

Presented in part at the 10th International Conference on AD and Related Disorders, Madrid, Spain, July 2006.

Received July 5, 2007. Accepted in final form October 22, 2007.

This article has been cited by other articles:

				E. P. Helzner, N. Scarmeas, S. Cosentino, M. X. Tang, N. Schupf, and Y. Stern Survival in Alzheimer disease: A multiethnic, population-based study of incident cases Neurology, November 4, 2008; 71(19): 1489 - 1495. [Abstract] [Full Text] [PDF]